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1.
Artigo em Inglês | MEDLINE | ID: mdl-38716207

RESUMO

Background: Deficient mismatch repair (MMR) leading to microsatellite instability (MSI) in tumors is thought to be present in over 15% of colorectal cancer (CRC) cases. Testing CRC for MSI has traditionally been recommended following the fulfillment of clinical criteria. However, the performance of clinical criteria, especially the family history, as a selection tool for MSI screening in CRC is questionable. Methods: We retrospectively investigated the incidence of high degree MSI (MSI-H) tumors in an unselected population of CRC patients and compared its prevalence between individuals with and without family history of cancers within the spectrum of MSI-H tumors as defined in the revised Bethesda criteria. Results: The study population included 274 patients, 70 with positive and 204 without family history of MSI-H tumors with complete data including findings from MSI analysis. The overall incidence of MSI-H CRC was 18.98%. There was no statistically significant difference in the incidence of MSI-H CRC amongst both groups. The sensitivity and specificity of family history with regard to the presence of an MSI-H tumor in this collective was 36.5% and 77.5%, respectively. Conclusions: A relevant number of cases with high MSI-H CRC may be missed secondary to screening based on clinical criteria like family history alone. Thus, systematic screening independent of clinical characteristics, especially family history of cancer should be recommended in all cases with CRC.

2.
Front Surg ; 11: 1288061, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601878

RESUMO

Background: Clinical guidelines suggest screening of colorectal cancer (CRC) for microsatellite instability (MSI). However, microsatellite instability-high (MSI-H) CRC is not rare in older patients. This study aimed to investigate the prevalence of MSI-H CRC in an unselected population in an age-based manner. Material and methods: A retrospective analysis of data from patients undergoing radical surgery for CRC was performed. Only cases with results from MSI testing using immunochemistry (IHC) were analyzed. Age-based analyses were performed using two cut-off ages: 50 years. as stated in Amsterdam II guidelines, and 60 years. as outlined in the revised Bethesda criteria. Results: The study population included 343 (146 female and 197 male) patients with a median age of 70 years (range 21-90 years). The prevalence of MSI-H tumors in the entire cohort was 18.7%. The prevalence of MSI-H CRC was 22.5% in the group ≤50 years vs. 18.2% in the group >50 years using the age limit in the Amsterdam II guidelines. MSI-H CRC was present in 12.6% of the group aged ≤60 years compared to 20.6% in the control group >60 years. Conclusion: MSI screening of CRC based on age alone is associated with negative selection of a relevant number of cases. MSI-H CRC is also common in elderly patients, who may be negatively selected secondary to an age-based screening algorithm. Following the results of this study, screening based on clinical criteria should be omitted in favor of systematic screening as is already internationally practiced.

3.
Cancers (Basel) ; 15(19)2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37835449

RESUMO

Lymph node metastases are common in pelvic urological tumors, and the age-related remodeling process of the pelvic lymph nodes influences metastatic behavior. The aim of this work is to characterize age-related degenerative changes in the pelvic lymph nodes with respect to their occurrence and extent. A total of 5173 pelvic lymph nodes of 390 patients aged 44 to 79 years (median 68 years, IQR 62-71 years) were histologically examined for degenerative structural changes. Lymph node size, lipomatous atrophy, capsular fibrosis, framework fibrosis, and calcifications were recorded semi-quantitatively and evaluated by age group. Significantly more lymph nodes <10 mm were found in older patients (p = 0.001). The incidence of framework fibrosis, capsular fibrosis, and calcifications increased significantly with increasing patient age (p < 0.001). In lipomatous atrophy, an increase in mild to moderate lipomatous atrophy was observed with increasing age (p < 0.001). In this, the largest study to date on this topic, age-related degenerative changes in pelvic lymph nodes were proven. Due to the consecutive decrease in hte filtration function of pelvic lymph nodes with increasing age, staging and therapy of metastatic pelvic urologic carcinomas should be reconsidered.

4.
J Med Internet Res ; 25: e49368, 2023 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-37865883

RESUMO

BACKGROUND: ChatGPT is a 175-billion-parameter natural language processing model that is already involved in scientific content and publications. Its influence ranges from providing quick access to information on medical topics, assisting in generating medical and scientific articles and papers, performing medical data analyses, and even interpreting complex data sets. OBJECTIVE: The future role of ChatGPT remains uncertain and a matter of debate already shortly after its release. This review aimed to analyze the role of ChatGPT in the medical literature during the first 3 months after its release. METHODS: We performed a concise review of literature published in PubMed from December 1, 2022, to March 31, 2023. To find all publications related to ChatGPT or considering ChatGPT, the search term was kept simple ("ChatGPT" in AllFields). All publications available as full text in German or English were included. All accessible publications were evaluated according to specifications by the author team (eg, impact factor, publication modus, article type, publication speed, and type of ChatGPT integration or content). The conclusions of the articles were used for later SWOT (strengths, weaknesses, opportunities, and threats) analysis. All data were analyzed on a descriptive basis. RESULTS: Of 178 studies in total, 160 met the inclusion criteria and were evaluated. The average impact factor was 4.423 (range 0-96.216), and the average publication speed was 16 (range 0-83) days. Among the articles, there were 77 editorials (48,1%), 43 essays (26.9%), 21 studies (13.1%), 6 reviews (3.8%), 6 case reports (3.8%), 6 news (3.8%), and 1 meta-analysis (0.6%). Of those, 54.4% (n=87) were published as open access, with 5% (n=8) provided on preprint servers. Over 400 quotes with information on strengths, weaknesses, opportunities, and threats were detected. By far, most (n=142, 34.8%) were related to weaknesses. ChatGPT excels in its ability to express ideas clearly and formulate general contexts comprehensibly. It performs so well that even experts in the field have difficulty identifying abstracts generated by ChatGPT. However, the time-limited scope and the need for corrections by experts were mentioned as weaknesses and threats of ChatGPT. Opportunities include assistance in formulating medical issues for nonnative English speakers, as well as the possibility of timely participation in the development of such artificial intelligence tools since it is in its early stages and can therefore still be influenced. CONCLUSIONS: Artificial intelligence tools such as ChatGPT are already part of the medical publishing landscape. Despite their apparent opportunities, policies and guidelines must be implemented to ensure benefits in education, clinical practice, and research and protect against threats such as scientific misconduct, plagiarism, and inaccuracy.


Assuntos
Inteligência Artificial , Análise de Dados , Humanos , Escolaridade , Idioma , Processamento de Linguagem Natural
5.
Z Gerontol Geriatr ; 56(4): 324-334, 2023 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-37306771

RESUMO

Prostate cancer is the most frequent cancer in men. For localized prostate cancer, surgery and radiotherapy are the standard treatment, with active surveillance also used in low-risk cases. For advanced/metastatic disease, androgen deprivation treatment is carried out. Further options include inhibitors of the androgen receptor axis and taxane-based chemotherapy. The avoidance of side effects should be considered, e.g., by dose adjustment. New options include poly(ADP-ribose) polymerase (PARP) inhibitors, and radioligand treatment. The existing guidelines only provide a few treatment recommendations for older patients; however, the treatment of older patients should primarily consider not only chronological age but also the patient's psychological and physical condition and preferences. In this context, the geriatric assessment represents an important instrument for determining the treatment strategy.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Idoso , Neoplasias da Próstata/terapia , Neoplasias da Próstata/tratamento farmacológico , Antagonistas de Androgênios/efeitos adversos
6.
BMC Urol ; 23(1): 6, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36609261

RESUMO

BACKGROUND: To evaluate the incidence of lymph node degeneration and its association with nodal metastatic pattern in prostate cancer. METHODS: A retrospective analysis of the submitted lymph node specimen of 390 prostatectomies in 2011 was performed. All lymph nodes were histologically re-evaluated and the degree of lymph node degeneration e.g. lipomatous atrophy, capsular and framework fibrosis, and calcifications as well as the lymph node size were recorded. Lymph node degeneration was compared in the anatomic regions of the pelvis as well as in lymph nodes with and without metastases of prostatic cancer. RESULTS: Eighty-one of 6026 lymph nodes demonstrated metastases. Complete histologic examination with analysis of a complete cross-section was possible in 5173 lymph nodes including all lymph nodes with metastases. The incidence of lymph node degeneration was different across the various landing sites. Lymph node metastases were primarily detected in less degenerative and therefore more functional lymph nodes. In metastatic versus non-metastatic lymph nodes low lipomatous atrophy was reported in 84.0% versus 66.7% (p = 0.004), capsular fibrosis in 14.8% versus 35.4% (p < 0.001), calcifications in 35.8% versus 46.1% (p = 0.072) and framework fibrosis in 69.8% versus 75.3% (p = 0.53). Metastases were also identified more frequently in larger than in smaller lymph nodes (63.0% vs. 47.5%; p = 0.007). CONCLUSIONS: Degenerative changes in pelvic lymph nodes are commonly detectable but occur with variable frequency in the various nodal landing sites in the pelvis. The degree of lymph node degeneration of single lymph nodes has a significant influence on whether a lymph node is infiltrated by tumor cells and may harbour metastases.


Assuntos
Linfonodos , Neoplasias da Próstata , Masculino , Humanos , Estudos Retrospectivos , Linfonodos/patologia , Neoplasias da Próstata/patologia , Pelve/patologia , Fibrose , Excisão de Linfonodo
7.
Artigo em Inglês | MEDLINE | ID: mdl-36012068

RESUMO

(1) Background: Injuries related to resuscitation are not usually systematically recorded and documented. By evaluating this data, conclusions could be drawn about the quality of the resuscitation, with the aim of improving patient care and safety. (2) Methods: We are planning to conduct a multicentric, retrospective 3-phased study consisting of (1) a worldwide literature review (scoping review), (2) an analysis of anatomical pathological findings from local institutions in North Rhine-Westphalia, Germany to assess the transferability of the review data to the German healthcare system, and (3) depending on the results, possibly establishing potential prospective indicators for resuscitation-related injuries as part of quality assurance measures. (3) Conclusions: From the comparison of literature and local data, the picture of resuscitation-related injuries will be focused on and quality indicators will be derived.


Assuntos
Reanimação Cardiopulmonar , Parada Cardíaca Extra-Hospitalar , Reanimação Cardiopulmonar/métodos , Alemanha , Humanos , Estudos Prospectivos , Estudos Retrospectivos
8.
Urol Int ; 106(8): 775-783, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34963122

RESUMO

INTRODUCTION: The aim of the study was to evaluate the effectiveness of a modified transvesical obturator nerve block (ONB) in the prevention of obturator nerve reflex and consecutive bladder perforations (BPs) during transurethral resection of bladder tumors (TURBTs). MATERIALS AND METHODS: A retrospective analysis of all patients resected in 2014-2015 due to a bladder tumor of the lateral walls, including a follow-up period until December 2018, was performed. Two groups were defined: in the first group, all patients underwent TURBT with a modified transvesical ONB. The second group underwent conventional TURBT with intermittent resection. Primary endpoints were the rates of adductor contractions and BPs. RESULTS: Ninety-four out of 1,145 resected patients presented with tumors on the lateral wall of the bladder and a complete dataset including a long-term follow-up. Thirty-six patients were treated in the ONB group, and 58 patients comprised the control group. The median age in the 2 groups was 70.8 and 71.8 years in the first and second groups, respectively. Adductor spasms were reported in 8.33 versus 25.86% (p = 0.057) and perforation in 2.78 versus 17.24% (p = 0.047) in groups 1 and 2, respectively. After a median follow-up of 32.5 months, there was no significant difference in recurrence rates (52.78 vs. 51.72%, p = 0.672). In a subgroup analysis, lower perforation rates were recorded for the ONB group in patients with tumors <3 cm (0/30 vs. 8/46, p = 0.076) and in patients with unifocal tumors (0/12 vs. 5/23, p = 0.141). DISCUSSION/CONCLUSION: The simplified approach of transvesical ONB demonstrated in this study appears to be an inexpensive, safe, effective, and simple-to-use technique.


Assuntos
Bloqueio Nervoso , Neoplasias da Bexiga Urinária , Idoso , Cistectomia/efeitos adversos , Cistectomia/métodos , Humanos , Bloqueio Nervoso/efeitos adversos , Bloqueio Nervoso/métodos , Nervo Obturador/patologia , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia
9.
Urol Oncol ; 39(5): 300.e7-300.e13, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33308977

RESUMO

PURPOSE: Bladder cancer is predominant in the elderly. Up to 70% of geriatric patients with muscle-invasive bladder cancer do not receive curative treatment. We analyzed the outcome of patients managed only by transurethral resection of bladder tumor (TURBT) without chemo- or radio-therapy, and performed a cost analysis of the cumulative inpatient interventions throughout the course of the disease. METHODS: From 2010 to 2016 81 patients ≥75 years with de novo muscle-invasive bladder cancer who were not eligible for curative treatment options were analyzed retrospectively. All patients were treated only with TURBT. Overall survival (OS) was measured by Kaplan-Meier plots (log-rank test) and clinical parameters predicting OS by a multivariate analysis. The cost analysis was based on actual billing from the hospital provider and referenced standardized pricing in Germany for bladder cancer treatment. RESULTS: The median age was 83 years. The OS was 11 months, the 1-year OS was 42%. In the multivariate model Charlson Comorbidity Index <8 (P = 0.016), tumor size ≤3 cm (P = 0.011), complete (T0) tumor resection (P = 0.003), normal C-reactive protein level (P = 0.010), and initial elective surgery (P = 0.035) were shown to be independent predictors of longer OS in palliative TURBT regimes. Median treatment cost for the TURBT regimen was $16,175 vs. $16,467 for a salvage radical cystectomy in this cohort. CONCLUSIONS: In a TURBT-only concept elective surgery, tumor size, Charlson Comorbidity Index, C-reactive protein level and complete TURBT are independent predictors of OS. The treatment-related cumulative cost appears to be higher in patients not managed by cystectomy.


Assuntos
Custos e Análise de Custo , Cistectomia/economia , Cistectomia/métodos , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Invasividade Neoplásica , Estudos Retrospectivos , Resultado do Tratamento , Uretra , Neoplasias da Bexiga Urinária/patologia
11.
Interact Cardiovasc Thorac Surg ; 28(3): 339-343, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30189016

RESUMO

OBJECTIVES: Resection of tumour spread on a very thin visceral pleura might be challenging, and collateral damage to the lung parenchyma might occur. We aimed to develop an operative technique, which might facilitate the parenchyma-sparing destruction of the visceral pleura. This experimental work investigated the effects of a neodymium:yttrium aluminum garnet (Nd:YAG) laser on the visceral pleura in an ex vivo porcine lung model. METHODS: We used a diode-pumped Nd:YAG laser (Limax® 120, KLS Martin, Tuttlingen, Germany) to investigate the effects on the visceral pleural in 20 porcine lungs. The laser was applied on a standardized length in 4 different settings: Group I (80 W, 6 s), Group II (80 W, 12 s), Group III (120 W, 6 s) and Group IV (120 W, 12 s). All specimens were analysed histologically. RESULTS: The mean thickness of the visceral pleura was 81 ± 10 µm. Increasing power levels and longer application duration resulted in significantly enhanced laser destruction effects. The mean depths of the carbonization zone were 142 ± 42 µm, 378 ± 137 µm, 607 ± 155 µm and 1371 ± 271 µm for Groups I-IV, respectively (P < 0.001). The ratio of carbonization zone to pleural thickness was measured for each section (C/P ratio) to quantify the thermal effects. The corresponding C/P ratio for Groups I-IV were 1.72 ± 0.55, 4.98 ± 1.96, 7.11 ± 1.61 and 17.35 ± 4.35, respectively (P < 0.001). CONCLUSIONS: Our study showed that increasing power levels and application duration of the laser lead to a significantly increased carbonization and destruction zones. Further in vivo human studies should evaluate the feasibility of laser application for a potential translational relevance for human use.


Assuntos
Hemostasia Cirúrgica/métodos , Terapia a Laser/métodos , Lasers de Estado Sólido/uso terapêutico , Pneumopatias/cirurgia , Pulmão/cirurgia , Pleura/cirurgia , Pneumonectomia/métodos , Alumínio , Animais , Modelos Animais de Doenças , Pulmão/patologia , Pleura/patologia , Suínos , Ítrio
12.
Oncotarget ; 9(43): 27256-27267, 2018 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-29930763

RESUMO

MicroRNAs (miRNAs) are ∼22-nt molecules exerting control of protein expression in cancer tissues. The current study determined the full spectrum of miRNA dysregulation in freshly isolated human colon or rectal cancer biopsies as well as in controls of healthy adjacent tissue (total of n = 100) using an Illumina sequencing technology. In this work, we aimed to identify miRNAs that may serve as future marker to discern between these two subtypes. DESeq2 analysis revealed 53 significantly dysregulated miRNAs in colon cancer, 67 miRNAs in rectal cancer, and 97 miRNAs in both at a Padj value < 0.05 and ≥ 10 read counts. 65% of miRNAs were upregulated in colon as well as rectal cancer. Highest significant dysregulation (Padj < 0.00001) was detected for hsa-miR-21-5p, -215-5p and -378a in both colon and rectal cancer. Among the group of miRNAs with Padj < 0.05 and more than 2-fold expression differences, hsa-miR-375 was detected in rectal cancer only, and hsa-miR-133a-3p only in colon cancer. Receiver operating characteristic (ROC) analysis confirmed highly distinct sensitivities for hsa-miR-375 to detect rectal cancer (area under the curve (AUC): 0.9), while hsa-miR-133a-3p (AUC: 0.89) had the highest sensitivity for detecting colon cancer. We conclude that hsa-miR-375 and hsa-miR-133a-3p may serve as new markers of rectal or colon cancer and should be further investigated to search for different etiologies of colorectal cancer.

13.
Int J Colorectal Dis ; 33(4): 403-409, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29520454

RESUMO

BACKGROUND: Colorectal cancer (CRC) is the second leading cause for cancer-related death in industrialized nations. Nodal involvement has been identified as a relevant prognostic feature in CRC. Extra nodal metastasis (ENM) describes the spread of malignant cells beyond the nodal capsule. ENM is thought to be an independent risk factor for poor survival. This study examined ENM as an independent risk factor for poor overall survival in patients with node-positive CRC. MATERIALS AND METHODS: Data from a prospectively maintained CRC database was retrospectively analyzed. Blinded slides of patients with stage III and IV CRC following radical surgical resection were re-examined for the presence of ENM. The effect of ENM on overall survival was examined using Kaplan-Meier curves. RESULTS: One hundred forty-seven cases with node-positive CRC (UICC stages III and IV) including 78 cases with ENM were included for analysis. ENM was seen in 60 patients with colon cancer (58.8%) and in 18 patients with rectal cancer (40%), p = 0.033. ENM-positive patients had a significantly higher odd for cancer-related death compared to ENM-negative patients ratio of [OR 0.44: 0.22-0.88, CI 95%, p = 0.021], p = 0.02. The median overall survival was significantly longer in patients without ENM, 51.0 ± 33 vs. 30.5 ± 42 months, p = 0.02. CONCLUSION: Extra nodal metastasis is an independent prognostic factor in patients with node-positive colorectal cancer. Extra nodal metastasis is associated with high odds of tumor-related mortality and poor overall survival.


Assuntos
Neoplasias Colorretais/patologia , Estimativa de Kaplan-Meier , Metástase Linfática/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Coloração e Rotulagem
14.
World J Emerg Surg ; 13: 9, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29467816

RESUMO

Background: Acute perforated cholecystitis (APC) is probably the most severe benign gallbladder pathology with high rates of morbidity and mortality. The cause of APC has not been fully understood. We postulated that APC is a complication of advanced gallbladder inflammation. The aim of this study was to investigate the extent of gallbladder inflammation in patients with APC. Methods: Patients with intraoperative and histopathologic diagnosis of APC were compared with cases with acute cholecystitis without perforation with respect to the extent of inflammation on histopathology as well as surgical outcomes. Results: Fifty patients with APC were compared to 150 cases without perforation. Advanced age > 65 years and elevated CRP were confirmed on multivariate analysis as independent risk factors for APC. Advanced gallbladder inflammation was seen significantly more often in patients with APC (84.0 vs. 18.7%). Surgery lasted significantly longer 131.3 ± 55.2 min vs. 100.4 ± 47.9 min; the rates of conversion (22 vs. 4%), morbidity (24 vs. 7%), and mortality (8 vs. 1%) were significantly higher in patients with APC. ICU management following surgery was needed significantly more often in the APC group (56 vs. 15%), and the overall length of stay (11.2 ± 12.0 days vs. 5.8 ± 6.5 days) was significantly longer compared to the group without perforation. Conclusion: Acute gallbladder perforation in patients with acute cholecystitis represents the most severe complication of cholecystitis. Acute perforated cholecystitis is a sequela of advanced gallbladder inflammation like empyematous and gangrenous cholecystitis and is associated with poor outcome compared to non-perforated cases.


Assuntos
Colecistectomia Laparoscópica/efeitos adversos , Colecistite Aguda/complicações , Perfuração Intestinal/etiologia , Idoso , Idoso de 80 Anos ou mais , Colecistite Aguda/mortalidade , Feminino , Vesícula Biliar/lesões , Vesícula Biliar/fisiopatologia , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Estudos Prospectivos , Fatores de Risco , Resultado do Tratamento
15.
Eur Urol Focus ; 4(6): 907-915, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-28753886

RESUMO

BACKGROUND: The first global lipidomic profiles associated with urothelial cancer of the bladder (UCB) and its clinical stages associated with progression were identified. OBJECTIVE: To identify lipidomic signatures associated with survival and different clinical stages of UCB. DESIGN, SETTING, AND PARTICIPANTS: Pathologically confirmed 165 bladder-derived tissues (126 UCB, 39 benign adjacent or normal bladder tissues). UCB tissues included Ta (n=16), T1 (n=30), T2 (n=43), T3 (n=27), and T4 (n=9); lymphovascular invasion (LVI) positive (n=52) and negative (n=69); and lymph node status N0 (n=28), N1 (n=11), N2 (n=9), N3 (n=3), and Nx (n=75). RESULTS AND LIMITATIONS: UCB tissues have higher levels of phospholipids and fatty acids, and reduced levels of triglycerides compared with benign tissues. A total of 59 genes associated with altered lipids in UCB strongly correlate with patient survival in an UCB public dataset. Within UCB, there was a progressive decrease in the levels of phosphatidylserine (PS), phosphatidylethanolamines (PEs), and phosphocholines, whereas an increase in the levels of diacylglycerols (DGs) with tumor stage. Transcript and protein expression of phosphatidylserine synthase 1, which converts DGs to PSs, decreased progressively with tumor stage. Levels of DGs and lyso-PEs were significantly elevated in tumors with LVI and lymph node involvement, respectively. Lack of carcinoma in situ and treatment information is the limitation of our study. CONCLUSIONS: To date, this is the first study describing the global lipidomic profiles associated with UCB and identifies lipids associated with tumor stages, LVI, and lymph node status. Our data suggest that triglycerides serve as the primary energy source in UCB, while phospholipid alterations could affect membrane structure and/or signaling associated with tumor progression. PATIENT SUMMARY: Lipidomic alterations identified in this study set the stage for characterization of pathways associated with these altered lipids that, in turn, could inform the development of first-of-its-kind lipid-based noninvasive biomarkers and novel therapeutic targets for aggressive urothelial cancer of the bladder.


Assuntos
Carcinoma de Células de Transição/metabolismo , Ácidos Graxos/metabolismo , Fosfolipídeos/metabolismo , Triglicerídeos/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/patologia , Estudos de Casos e Controles , Cromatografia Líquida , Biologia Computacional , Diglicerídeos/metabolismo , Feminino , Humanos , Metabolismo dos Lipídeos/genética , Linfonodos/patologia , Lisofosfolipídeos/metabolismo , Masculino , Espectrometria de Massas , Invasividade Neoplásica , Estadiamento de Neoplasias , Transferases de Grupos Nitrogenados/genética , Transferases de Grupos Nitrogenados/metabolismo , Fosfatidiletanolaminas/metabolismo , Fosfatidilserinas/metabolismo , Fosforilcolina/metabolismo , Análise de Componente Principal , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
16.
Mini Rev Med Chem ; 18(13): 1133-1142, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-26975667

RESUMO

Locally advanced, muscle-invasive urothelial carcinoma of the bladder (MIBC) may be definitively treated with either radiotherapy or radical cystectomy (RC) with urinary diversion. Neoadjuvant chemotherapy (NAC) is typically administered prior to treatment with either modality. Receiving NAC prior to RC might confer a survival advantage compared to undergoing RC alone. However, its usefulness has been questioned due to concerns about over treatment and toxicity. Having the ability to predict whether individual patients would benefit from or be harmed by NAC would be an important tool in precision medicine. Unfortunately, to date no prognostic or predictive molecular markers have been validated for this purpose. In this manuscript, we review the current state of molecular markers in MIBC treatment and outline how recent advances in whole-genome sequencing may soon improve the selection of precisely targeted therapeutics for the benefit of individual patients.


Assuntos
Antineoplásicos/uso terapêutico , Terapia Neoadjuvante , Neoplasias da Bexiga Urinária/terapia , Antineoplásicos/química , Biomarcadores Tumorais/metabolismo , Proteínas de Ciclo Celular/metabolismo , Receptores ErbB/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Proteínas de Choque Térmico/metabolismo , Humanos , Neoplasias da Bexiga Urinária/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
17.
Cancer Prev Res (Phila) ; 10(10): 588-597, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28851690

RESUMO

Smoking is a major risk factor for the development of bladder cancer; however, the functional consequences of the carcinogens in tobacco smoke and bladder cancer-associated metabolic alterations remain poorly defined. We assessed the metabolic profiles in bladder cancer smokers and non-smokers and identified the key alterations in their metabolism. LC/MS and bioinformatic analysis were performed to determine the metabolome associated with bladder cancer smokers and were further validated in cell line models. Smokers with bladder cancer were found to have elevated levels of methylated metabolites, polycyclic aromatic hydrocarbons, DNA adducts, and DNA damage. DNA methyltransferase 1 (DNMT1) expression was significantly higher in smokers than non-smokers with bladder cancer. An integromics approach, using multiple patient cohorts, revealed strong associations between smokers and high-grade bladder cancer. In vitro exposure to the tobacco smoke carcinogens, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and benzo[a]pyrene (BaP) led to increase in levels of methylated metabolites, DNA adducts, and extensive DNA damage in bladder cancer cells. Cotreatment of bladder cancer cells with these carcinogens and the methylation inhibitor 5-aza-2'-deoxycytidine rewired the methylated metabolites, DNA adducts, and DNA damage. These findings were confirmed through the isotopic-labeled metabolic flux analysis. Screens using smoke-associated metabolites and DNA adducts could provide robust biomarkers and improve individual risk prediction in bladder cancer smokers. Noninvasive predictive biomarkers that can stratify the risk of developing bladder cancer in smokers could aid in early detection and treatment. Cancer Prev Res; 10(10); 588-97. ©2017 AACR.


Assuntos
Biomarcadores Tumorais/urina , Carcinógenos/toxicidade , Dano ao DNA/efeitos dos fármacos , Metilação de DNA/efeitos dos fármacos , Mutagênicos/toxicidade , Nicotiana/toxicidade , Fumar/efeitos adversos , Produtos do Tabaco/toxicidade , Neoplasias da Bexiga Urinária/metabolismo , Azacitidina/análogos & derivados , Azacitidina/farmacologia , Benzo(a)pireno/toxicidade , Butanonas/sangue , Carcinógenos/análise , Linhagem Celular Tumoral , Estudos de Coortes , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , Adutos de DNA/sangue , Decitabina , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Masculino , Metaboloma/efeitos dos fármacos , Metabolômica/métodos , Mutagênicos/análise , Gradação de Tumores , Nitrosaminas/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/sangue , Hidrocarbonetos Policíclicos Aromáticos/urina , Medição de Risco/métodos , Fumar/sangue , Fumar/urina , Nicotiana/química , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/terapia , Neoplasias da Bexiga Urinária/urina
19.
PLoS One ; 11(12): e0168769, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28033410

RESUMO

BACKGROUND: Is the patient really suffering from acute appendicitis? Right lower quadrant pain is the most common sign of acute appendicitis. However, many other bowels pathologies might mimic acute appendicitis. Due to fear of the consequences of delayed or missed diagnosis, the indication for emergency appendectomy is liberally made. This has been shown to be associated with high rates of negative appendectomy with risk of potentially serious or lethal complications. Thus there is need for a better preoperative screening of patients with suspected appendicitis. METHODS: This prospective single center single-blinded pilot study was conducted in the Department of surgery at the HELIOS Universitätsklinikum Wuppertal, Germany. Calprotectin was measured in pre-therapeutic stool samples of patients presenting in the emergency department with pain to the right lower quadrant. Fecal calprotectin (FC) values were analyzed using commercially available ELISA kits. Cut-off values for FC were studied using the receiver-operator characteristic (ROC) curve. The Area under the curve (AUC) was reported for each ROC curve. RESULTS: The mean FC value was 51.4 ± 118.8 µg/g in patients with AA, 320.9 ± 416.6 µg/g in patients with infectious enteritis and 24.8 ± 27.4 µg/g in the control group. ROC curve showed a close to 80% specificity and sensitivity of FC for AA at a cut-off value of 51 µg/g, AUC = 0.7. The sensitivity of FC at this cut-off value is zero for enteritis with a specificity of 35%. CONCLUSION: Fecal calprotectin could be helpful in screening patients with pain to the right lower quadrant for the presence of acute appendicitis or infectious enteritis with the aim of facilitating clinical decision-making and reducing the rate of negative appendectomy.


Assuntos
Apendicite/diagnóstico , Apendicite/metabolismo , Fezes/química , Complexo Antígeno L1 Leucocitário/análise , Período Pré-Operatório , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Curva ROC , Adulto Jovem
20.
J Transl Med ; 14(1): 107, 2016 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-27118309

RESUMO

BACKGROUND: Acute appendicitis is a common cause for a visit to the emergency department and appendectomy represents the most common emergency procedure in surgery. The rate of negative appendectomy however has remained high despite modern diagnostic apparatus. Therefore, there is need for a better preoperative screening of patients with suspected appendicitis. Calprotectin represents a predominant protein in the cytosol of neutrophil granulocytes and has been extensively investigated with regard to bowel pathologies. This study investigates the expression of calprotectin in the lumen of the vermiform appendix of patients undergoing appendectomy for suspected appendicitis. METHODS: Appendix specimens from patients undergoing emergency appendectomy for suspected acute appendicitis were examined. Acute appendicitis was confirmed on histopathology. The qualitative expression of calprotectin in the vermiform appendix specimens was analyzed using specific calprotectin antibodies. RESULTS: Vermiform appendix specimens from 52 patients (22 female and 30 male) including 11 with uncomplicated and 41 with complicated appendicitis were analyzed. Strong immunostainings were achieved with calprotectin antibody in the lumen of all specimens irrespective of the extent of appendicitis. Immunostaining was negative in the uninflamed appendix. CONCLUSIONS: High calprotectin activity could be demonstrated within the lumen of vermiform appendix specimens following appendectomy for acute appendicitis. The high luminal accumulation of calprotectin-carrying cells could be interpreted as an invitation to study the expression of calprotectin in stool as a new diagnostic aid in patients with suspected appendicitis.


Assuntos
Apendicite/metabolismo , Complexo Antígeno L1 Leucocitário/metabolismo , Doença Aguda , Adolescente , Adulto , Idoso , Anticorpos/metabolismo , Apendicite/patologia , Apêndice/metabolismo , Apêndice/patologia , Biomarcadores/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Adulto Jovem
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